The overall goal of these four interlocking and cooperative projects is to study the cellular and molecular basis of experimental and human autoimmune disease. Serologic, cellular, biochemical and molecular biology techniques will be used to analyze the genes and their products encoding the specificity of autoantibodies in patients with scleroderma and bowel diseases, class II antigens, as well as of critical molecules which play an important role in the cell cooperation such as the Fc receptor. Furthermore, cell cooperation between antigens presenting cells and major subpopulations of lymphocytes mediating either humoral or cellular autoimmune response will be studied by cellular, biochemical and molecular biology approaches. Each individual project has a major aim to provide important insights in the pathogenesis of autoimmune disease.